It has been known for more than a decade that macromolecules can be taken up by mammalian cells. Only recently did it become apparent that proteins and polynucleotides can exert critical functions in host cells. In spite of the importance of the problem, little work has been focused upon the physiology and control of macromolecular uptake, and upon the factors that influence the fate and expression of ingested macromolecules. As pointed out elsewhere, the field is still an underdeveloped area. We plan to take an active part in its development. Quantitative assays have been worked out to measure the net uptake and the intracellular breakdown of I131-albumin in cultured cells. It has been found that basic polymers (basic polyamino acids, DEAE-dextran) will markedly enhance albumin uptake. The mechanisms and the morphological correlate of this effect are still unknown and require investigation. It has been shown that different proteins are taken up at different rates, but the parameters that define selectivity have not so far been studied in a systematic fashion. The use of synthetic copolymers of known structure should provide an appropriate tool to clarify this problem. It has been establish that proteins, once ingested, are subjected to intensive intracellular digestion and must escape this process in order to expres biological functions. The factors that influence this balance are poorly defined and will be investigated. They are of considerable interest to biologists concerned with antigen uptake, genetic transformation and genetic therapy.